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Synthesis of neuraminidase-resistant sialoside-modified three-way junction DNA and its binding ability to various influenza viruses

Yamabe, Miyuki, Fujita, Akira, Kaihatsu, Kunihiro, Ebara, Yasuhito
Carbohydrate research 2019 v.474 pp. 43-50
DNA, Orthomyxoviridae, binding capacity, binding sites, glycosides, hemagglutinins, sialidase, viruses
Natural sialic acid-modified compounds are capable of targeting influenza virus hemagglutinin (HA). However, these compounds have limited inhibitory effect because natural O-glycoside bond in these compounds are prone to be cleaved by neuraminidase (NA) on the surface of viruses. In this study, we synthesized NA-resistant sialoside that included unnatural S-glycoside bonds and modified this sialoside on a three-way junction (3WJ) DNA to display complementary distribution to its binding sites on a HA trimer. This S-glycoside-containing sialoside-modified 3WJ DNA showed certain NA resistance and maintained high binding affinity. Importantly, our observations showed that substituting natural O-glycoside with unnatural S-glycoside did not affect the binding affinity of the sialoside-modified 3WJ DNA for viruses. Thus, this study is an important step forward in the development of NA-resistant sialoside derivatives for more effective detection and inhibition of infection by a broad spectrum of viruses.